Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Philippe Lesnik, … , Christopher A. Haskell, Israel F. Charo
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):333-340. https://doi.org/10.1172/JCI15555.
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Article Vascular biology

Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis

Abstract

The hallmark of early atherosclerosis is the accumulation of lipid-laden macrophages in the subendothelial space. Circulating monocytes are the precursors of these “foam cells,” and recent evidence suggests that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes. A polymorphism in the FK receptor, CX3CR1, has been linked to a decrease in the incidence of coronary artery disease. To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX3CR1 and crossed these mice into the apoE–/– background. Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE–/– mice on a high-fat diet. CX3CR1–/– mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis.

Authors

Philippe Lesnik, Christopher A. Haskell, Israel F. Charo

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Atherosclerotic lesion areas in CX3CR1+/+, apoE–/– and CX3CR1–/–, apoE–/...
Atherosclerotic lesion areas in CX3CR1+/+, apoE–/– and CX3CR1–/–, apoE–/– mice fed the Western diet for 5, 10, or 15 weeks. Each symbol depicts the percentage of the aorta that stained for lipid with Sudan IV in a single mouse. (a) Total aorta. Lesions in the CX3CR1–/– mice were significantly smaller than in CX3CR1+/+ mice at each timepoint (43%, 49%, and 36% reduced at 5, 10, and 15 weeks, respectively). (b) Aortic arch. Lesions were smaller in the CX3CR1–/– mice at each of the timepoints (29%, 40%, and 11% reduced at 5, 10, and 15 weeks, respectively). (c) Thoracic and abdominal aorta. Lesions were smaller in the CX3CR1–/– mice at each of the timepoints (56%, 60%, and 72% reduced at 5, 10, and 15 weeks, respectively). The horizontal bars represent the mean values for the group. *P ≤ 0.02, **P ≤ 0.002 vs. wild type.